Fluorescent dyes that operate in the long visible / near infra-red (NIR) region of the electromagnetic spectrum are excellent reporter components of in vivo targeting molecular probes, fluorescent ligands, enzyme substrates and general tracers. Such dyes are in very short supply at the present time and those that are commercially available are very expensive or are only available under severely restrictive license agreements. Many of the available dyes have undesirable properties such as relatively high non-specific binding and a tendency to aggregate and are prohibitively expensive due in part to unoptimized synthetic methods and inadequate molecular design. The main focus of this work is to discover novel, long wavelength near-infrared dyes that are designed for use in biomedical in vivo imaging, high throughput screening and other applicable techniques such as immunofluorescence microscopy, fluorescence resonance energy transfer and fluorescence activated cell sorting and counting. Developments in imaging technologies have had a profound impact on clinical medicine including, ultrasound scanning, magnetic resonance imaging, x-ray computed tomography and nuclear tomography imaging. These systems are primarily used for displaying anatomical, physiological and metabolic parameters but they are increasingly being used in experimental animal systems for imaging at the cellular and molecular levels in vivo. These currently used imaging systems rely on physical parameters and properties to generate image contrast such as, sound impedance, electromagnetic wave impedance or nuclear alignments. In vivo fluorescence imaging offers more sensitive early stage detection of tumors that is very difficult to achieve with existing imaging techniques. Novel synthetic chemistry pathways will be developed that will allow gram-scale synthesis of the dyes in high purity and will result in products that will be more widely available to the research and scientific community.